Brain Networks In Children Research Articles

Differential reconfiguration of brain networks in children in response to standard versus rewarded go/no-go task demands.

Response inhibition and sustained attention are critical for higher-order cognition and rely upon specific patterns of functional brain network organization. This study investigated how functional brain networks reconfigure to execute these cognitive processes during a go/no-go task with and without the presence of rewards in 26 children between the ages of 8 and 12 years. First, we compared task performance between standard and rewarded versions of a go/no-go task. We found that the presence of rewards reduced commission error rate, a measure considered to indicate improved response inhibition. Tau, thought to index sustained attention, did not change across task conditions. Next, changes in functional brain network organization were assessed between the resting state, the standard go/no-go task, and the rewarded go/no-go task. Relative to the resting state, integration decreased and segregation increased during the standard go/no-go task. A further decrease in integration and increase in segregation was observed when rewards were introduced. These patterns of reconfiguration were present globally and across several key brain networks of interest, as well as in individual regions implicated in the processes of response inhibition, attention, and reward processing. These findings align with patterns of brain network organization found to support the cognitive strategy of sustained attention, rather than response inhibition, during go/no-go task performance and suggest that rewards enhance this organization. Overall, this study used large-scale brain network organization and a within-subjects multi-task design to examine different cognitive strategies and the influence of rewards on response inhibition and sustained attention in late childhood.

Distinct structural brain network properties in children with familial versus non-familial attention-deficit/hyperactivity disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is among the most prevalent, inheritable, and heterogeneous childhood-onset neurodevelopmental disorders. Children with a hereditary background of ADHD have heightened risk of having ADHD and persistent impairment symptoms into adulthood. These facts suggest distinct familial-specific neuropathological substrates in ADHD that may exist in anatomical components subserving attention and cognitive control processing pathways during development. The objective of this study is to investigate the topological properties of the gray matter (GM) structural brain networks in children with familial ADHD (ADHD-F), non-familial ADHD (ADHD-NF), as well as matched controls. A total of 452 participants were involved, including 132, 165 and 155 in groups of ADHD-F, ADHD-NF and typically developed children, respectively. The GM structural brain network was constructed for each group using graph theoretical techniques with cortical and subcortical structures as nodes and correlations between volume of each pair of the nodes within each group as edges, while controlled for confounding factors using regression analysis. Relative to controls, children in both ADHD-F and ADHD-NF groups showed significantly higher nodal global and nodal local efficiencies in the left caudal middle frontal gyrus. Compared to controls and ADHD-NF, children with ADHD-F showed distinct structural network topological patterns associated with right precuneus (significantly higher nodal global efficiency and significantly higher nodal strength), left paracentral gyrus (significantly higher nodal strength and trend toward significantly higher nodal local efficiency) and left putamen (significantly higher nodal global efficiency and trend toward significantly higher nodal local efficiency). Our results for the first time in the field provide evidence of familial-specific structural brain network alterations in ADHD, that may contribute to distinct clinical/behavioral symptomology and developmental trajectories in children with ADHD-F.

Sex-related patterns of functional brain networks in children and adolescents with autism spectrum disorder.

Although numerous studies have emphasized the male predominance in autism spectrum disorder (ASD), how sex differences are related to the topological organization of functional networks remains unclear. This study utilized imaging data from 86 ASD (43 females, aged 7-18 years) and 86 typically developing controls (TCs) (43 females, aged 7-18 years) obtained from Autism Brain Imaging Data Exchange databases, constructed individual whole-brain functional networks, used a graph theory analysis to compute topological metrics, and assessed sex-related differences in topological metrics using a 2 × 2 factorial design. At the global level, females with ASD exhibited significantly higher cluster coefficient and local efficiency than female TCs, while no significant difference was observed between males with ASD and male TCs. Meanwhile, the neurotypical sex differences in cluster coefficient and local efficiency observed in TCs were not present in ASD. At the nodal level, ASD exhibited abnormal nodal centrality in the left middle temporal gyrus.

Resting-state functional connectivity in children cooled for neonatal encephalopathy.

Therapeutic hypothermia improves outcomes following neonatal hypoxic-ischaemic encephalopathy, reducing cases of death and severe disability such as cerebral palsy compared with normothermia management. However, when cooled children reach early school-age, they have cognitive and motor impairments which are associated with underlying alterations to brain structure and white matter connectivity. It is unknown whether these differences in structural connectivity are associated with differences in functional connectivity between cooled children and healthy controls. Resting-state functional MRI has been used to characterize static and dynamic functional connectivity in children, both with typical development and those with neurodevelopmental disorders. Previous studies of resting-state brain networks in children with hypoxic-ischaemic encephalopathy have focussed on the neonatal period. In this study, we used resting-state fMRI to investigate static and dynamic functional connectivity in children aged 6-8 years who were cooled for neonatal hypoxic-ischaemic without cerebral palsy [n = 22, median age (interquartile range) 7.08 (6.85-7.52) years] and healthy controls matched for age, sex and socioeconomic status [n = 20, median age (interquartile range) 6.75 (6.48-7.25) years]. Using group independent component analysis, we identified 31 intrinsic functional connectivity networks consistent with those previously reported in children and adults. We found no case-control differences in the spatial maps of these intrinsic connectivity networks. We constructed subject-specific static functional connectivity networks by measuring pairwise Pearson correlations between component time courses and found no case-control differences in functional connectivity after false discovery rate correction. To study the time-varying organization of resting-state networks, we used sliding window correlations and deep clustering to investigate dynamic functional connectivity characteristics. We found k = 4 repetitively occurring functional connectivity states, which exhibited no case-control differences in dwell time, fractional occupancy or state functional connectivity matrices. In this small cohort, the spatiotemporal characteristics of resting-state brain networks in cooled children without severe disability were too subtle to be differentiated from healthy controls at early school-age, despite underlying differences in brain structure and white matter connectivity, possibly reflecting a level of recovery of healthy resting-state brain function. To our knowledge, this is the first study to investigate resting-state functional connectivity in children with hypoxic-ischaemic encephalopathy beyond the neonatal period and the first to investigate dynamic functional connectivity in any children with hypoxic-ischaemic encephalopathy.

Localized alterations in cortical thickness and sulcal depth of the cingulo-opercular network in relation to lower reading fluency skills in children with dyslexia

The traditional models of reading development describe how language processing and word decoding contribute to reading comprehension and how impairments in word decoding, a defining feature of dyslexia, affect reading comprehension outcomes. However, these models do not include word and sentence reading (contextual reading) fluency, both of which engage executive functions, with notably decreased performance in children with dyslexia. In the current study, we compared cortical thickness and sulcal depth (CT/SD) in the cingulo-opercular (CO) executive functions brain network in children with dyslexia and typical readers and examined associations with word vs. contextual reading fluency. Overall, CT was lower in insular regions and higher in parietal and caudal anterior cingulate cortex regions in children with dyslexia. Children with dyslexia showed positive correlations between word reading fluency and CT/SD in insular regions, whereas no significant correlations were observed in typical readers. For sentence reading fluency, negative correlations with CT/SD were found in insular regions in children with dyslexia, while positive correlations with SD were found in insular regions in typical readers. These results demonstrate the differential relations between word and sentence reading fluency and anatomical circuitry supporting executive functions in children with dyslexia vs. typical readers. It also suggests that word and sentence reading fluency, relate to morphology of executive function-related regions in children with dyslexia, whereas in typical readers, only sentence reading fluency relates to morphology of executive function regions. The results also highlight the role of the insula within the CO network in reading fluency. Here we suggest that word and sentence reading fluency are distinct components of reading that should each be included in the Simple View of Reading traditional model.

Maternal positive mental health during pregnancy impacts the hippocampus and functional brain networks in children

Maternal positive mental health during pregnancy impacts the hippocampus and functional brain networks in children

Early life factors and structural brain network in children with overweight/obesity: The ActiveBrains project.

The aims of this study were to investigate the association of early life factors, including birth weight, birth length, and breastfeeding practices, with structural brain networks; and to test whether structural brain networks associated with early life factors were also associated with academic performance in children with overweight/obesity (OW/OB). 96 children with OW/OB aged 8-11 years (10.03 ± 1.16) from the ActiveBrains project were included. Early life factors were collected from birth records and reported by parents as weight, height, and months of breastfeeding. T1-weighted images were used to identify structural networks using a non-negative matrix factorization (NNMF) approach. Academic performance was evaluated by the Woodcock-Muñoz standardized test battery. Birth weight and birth length were associated with seven networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate nucleus, putamen, pallidum, nucleus accumbens, and amygdala. No associations were found for breastfeeding practices. None of the networks linked to birth weight and birth length were linked to academic performance. Birth weight and birth length, but not breastfeeding, were associated with brain structural networks in children with OW/OB. Thus, early life factors are related to brain networks, yet a link with academic performance was not observed. Birth weight and birth length, but not breastfeeding, were associated with several structural brain networks involving the cerebellum, cingulate gyrus, occipital pole, and subcortical structures including hippocampus, caudate, putamen, pallidum, accumbens and amygdala in children with overweight/obesity, playing a role for a normal brain development. Despite no academic consequences, other behavioral consequences should be investigated. Interventions aimed at improving optimal intrauterine growth and development may be of importance to achieve a healthy brain later in life.

2 Effects of Early Exposure to More Than One Language in the Home on Language Skills and Brain Functional Network Organization in Young Children with Autism Spectrum Disorder

Objective:Concerns that exposure to more than one language in the home might negatively impact language development in young children with autism spectrum disorder (ASD) are common among caregivers. Although research directly examining the impact of a multilingual home environment in ASD is scarce, emerging evidence shows that language outcomes might be equivalent or better in children with ASD exposed to more than one language (Romero & Uddin, 2021). However, no evidence to date exists on whether exposure to more than one language affects early brain functional development in children with ASD. The current study aims to examine the (1) cross-sectional and (2) longitudinal associations between home language environment (exposure to one v. multiple languages at home, H1l vs. H>1l) and receptive and expressive language skills in young children with and without ASD, and (3) to investigate links between home language environment and brain functional network organization.Participants and Methods:Participants included young children with ASD (n=67, mean age: 35±13 months, H>1l n=43) and typically developing (TD) children (n=39, mean age: 32±16 months, H>1l n=17) enrolled in a longitudinal study of early brain markers of autism. A subset of children with ASD for whom longitudinal behavioral data from two study visits were available (n=21, H>1l n=11) were used for exploratory analysis. Receptive language (RL) and expressive language (EL) skills were assessed by the Mullen Scales of Early Learning at each study visit. Data from 42 children with ASD (H>1l n=27) and 38 TD children (H>1l n= 15) for whom functional MRI data were acquired during natural sleep were included in functional connectivity (FC) analysis. ANCOVAs were employed to examine the effect of diagnosis, home language environment (H1l vs. H>1l) and its interaction on RL and EL skills while controlling for socioeconomic variables (i.e., maternal education level, income-to-needs ratio) and gestational age at birth. Linear mixed models were applied to explore the longitudinal effect of home language environment on RL and EL skills across two study visits in the ASD group. Lastly, FC analysis was conducted to compare functional connectivity across 7 canonical brain networks in children with and without ASD who were raised in H1l and H>1l.Results:We found significant diagnosis by home language environment interaction effect on EL skills, with children with ASD and H1l exhibiting the lowest EL skills. Longitudinal analysis identified a significant home language environment by study visit interaction effect on EL skills in children with ASD. Specifically, children with ASD and H1l showed lower EL skills at study visit 1 but equivalent EL skills at study visit 2 compared to children with ASD and H>1l. FC analysis revealed that children with ASD and H>1l displayed more typical brain network organization (similar to TD children) compared to those with H1l, specifically for FC between language, frontoparietal, and default mode networks.Conclusions:These results suggest that early exposure to more than one language in the home may be linked with better expressive language skills in young children with ASD. Results of functional connectivity analysis also suggest that exposure to more than one language may be associated with more neurotypical functional network organization, particularly involving language and high-order networks.

Abnormal structural and functional network topological properties associated with left prefrontal, parietal, and occipital cortices significantly predict childhood TBI-related attention deficits: A semi-supervised deep learning study.

Traumatic brain injury (TBI) is a major public health concern in children. Children with TBI have elevated risk in developing attention deficits. Existing studies have found that structural and functional alterations in multiple brain regions were linked to TBI-related attention deficits in children. Most of these existing studies have utilized conventional parametric models for group comparisons, which have limited capacity in dealing with large-scale and high dimensional neuroimaging measures that have unknown nonlinear relationships. Nevertheless, none of these existing findings have been successfully implemented to clinical practice for guiding diagnoses and interventions of TBI-related attention problems. Machine learning techniques, especially deep learning techniques, are able to handle the multi-dimensional and nonlinear information to generate more robust predictions. Therefore, the current research proposed to construct a deep learning model, semi-supervised autoencoder, to investigate the topological alterations in both structural and functional brain networks in children with TBI and their predictive power for post-TBI attention deficits. Functional magnetic resonance imaging data during sustained attention processing task and diffusion tensor imaging data from 110 subjects (55 children with TBI and 55 group-matched controls) were used to construct the functional and structural brain networks, respectively. A total of 60 topological properties were selected as brain features for building the model. The model was able to differentiate children with TBI and controls with an average accuracy of 82.86%. Functional and structural nodal topological properties associated with left frontal, inferior temporal, postcentral, and medial occipitotemporal regions served as the most important brain features for accurate classification of the two subject groups. Post hoc regression-based machine learning analyses in the whole study sample showed that among these most important neuroimaging features, those associated with left postcentral area, superior frontal region, and medial occipitotemporal regions had significant value for predicting the elevated inattentive and hyperactive/impulsive symptoms. Findings of this study suggested that deep learning techniques may have the potential to help identifying robust neurobiological markers for post-TBI attention deficits; and the left superior frontal, postcentral, and medial occipitotemporal regions may serve as reliable targets for diagnosis and interventions of TBI-related attention problems in children.

Neurofeedback Effects on EEG Connectivity among Children with Reading Disorders: I. Coherence

Electroencephalograms (EEGs) of children with reading disorders (RDs) are characterized by a higher theta and a lower alpha than those of typically developing children. Neurofeedback (NFB) may be helpful for treating learning disorders by reinforcing a reduction in the theta/alpha ratio. Several studies have suggested that NFB may lead to EEG power normalization and cognitive improvements. To further explore brain changes in isolated areas, the aim of this study was to explore the effects of an NFB protocol on functional connectivity (coherence) among children with RDs. Twenty children with an RD and an abnormally high theta/alpha ratio underwent 30 NFB sessions, and five children with the same characteristics received a sham NFB treatment. On average, the children in the NFB group showed an increase in reading accuracy and comprehension scores; their coherence diminished in the delta, theta, and beta bands and increased in the alpha band, primarily the theta intrahemispheric coherences of the left hemisphere, which is closely associated with reading. In contrast, children who received the sham NFB treatment did not show reading changes and had few changes in their coherence patterns. These preliminary results suggest that NFB can positively impact reading-related functions in the brain networks of children with RDs.

Inter-individual heterogeneity of functional brain networks in children with autism spectrum disorder

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical heterogeneity. This study aimed to explore the heterogeneity of ASD based on inter-individual heterogeneity of functional brain networks.MethodsResting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange database were used in this study for 105 children with ASD and 102 demographically matched typical controls (TC) children. Functional connectivity (FC) networks were first obtained for ASD and TC groups, and inter-individual deviation of functional connectivity (IDFC) from the TC group was then calculated for each individual with ASD. A k-means clustering algorithm was used to obtain ASD subtypes based on IDFC patterns. The FC patterns were further compared between ASD subtypes and the TC group from the brain region, network, and whole-brain levels. The relationship between IDFC and the severity of clinical symptoms of ASD for ASD subtypes was also analyzed using a support vector regression model.ResultsTwo ASD subtypes were identified based on the IDFC patterns. Compared with the TC group, the ASD subtype 1 group exhibited a hypoconnectivity pattern and the ASD subtype 2 group exhibited a hyperconnectivity pattern. IDFC for ASD subtype 1 and subtype 2 was found to predict the severity of social communication impairments and the severity of restricted and repetitive behaviors in ASD, respectively.LimitationsOnly male children were selected for this study, which limits the ability to study the effects of gender and development on ASD heterogeneity.ConclusionsThese results suggest the existence of subtypes with different FC patterns in ASD and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD.

Attenuated effective connectivity of large-scale brain networks in children with autism spectrum disorders.

Understanding the neurological basis of autism spectrum disorder (ASD) is important for the diagnosis and treatment of this mental disorder. Emerging evidence has suggested aberrant functional connectivity of large-scale brain networks in individuals with ASD. However, whether the effective connectivity which measures the causal interactions of these networks is also impaired in these patients remains unclear. The main purpose of this study was to investigate the effective connectivity of large-scale brain networks in patients with ASD during resting state. The subjects were 42 autistic children and 127 age-matched normal children from the ABIDE II dataset. We investigated effective connectivity of 7 large-scale brain networks including visual network (VN), default mode network (DMN), cerebellum, sensorimotor network (SMN), auditory network (AN), salience network (SN), frontoparietal network (FPN), with spectral dynamic causality model (spDCM). Parametric empirical Bayesian (PEB) was used to perform second-level group analysis and furnished group commonalities and differences in effective connectivity. Furthermore, we analyzed the correlation between the strength of effective connectivity and patients' clinical characteristics. For both groups, SMN acted like a hub network which demonstrated dense effective connectivity with other large-scale brain network. We also observed significant causal interactions within the "triple networks" system, including DMN, SN and FPN. Compared with healthy controls, children with ASD showed decreased effective connectivity among some large-scale brain networks. These brain networks included VN, DMN, cerebellum, SMN, and FPN. In addition, we also found significant negative correlation between the strength of the effective connectivity from right angular gyrus (ANG_R) of DMN to left precentral gyrus (PreCG_L) of SMN and ADOS-G or ADOS-2 module 4 stereotyped behaviors and restricted interest total (ADOS_G_STEREO_BEHAV) scores. Our research provides new evidence for the pathogenesis of children with ASD from the perspective of effective connections within and between large-scale brain networks. The attenuated effective connectivity of brain networks may be a clinical neurobiological feature of ASD. Changes in effective connectivity of brain network in children with ASD may provide useful information for the diagnosis and treatment of the disease.

Alterations in brain networks in children with sub-threshold autism spectrum disorder: A magnetoencephalography study.

Individuals with sub-threshold autism spectrum disorder (ASD) are those who have social communication difficulties but do not meet the full ASD diagnostic criteria. ASD is associated with an atypical brain network; however, no studies have focused on sub-threshold ASD. Here, we used the graph approach to investigate alterations in the brain networks of children with sub-threshold ASD, independent of a clinical diagnosis. Graph theory is an effective approach for characterizing the properties of complex networks on a large scale. Forty-six children with ASD and 31 typically developing children were divided into three groups (i.e., ASD-Unlikely, ASD-Possible, and ASD-Probable groups) according to their Social Responsiveness Scale scores. We quantified magnetoencephalographic signals using a graph-theoretic index, the phase lag index, for every frequency band. Resultantly, the ASD-Probable group had significantly lower small-worldness (SW) in the delta, theta, and beta bands than the ASD-Unlikely group. Notably, the ASD-Possible group exhibited significantly higher SW than the ASD-Probable group and significantly lower SW than the ASD-Unlikely group in the delta band only. To our knowledge, this was the first report of the atypical brain network associated with sub-threshold ASD. Our findings indicate that magnetoencephalographic signals using graph theory may be useful in detecting sub-threshold ASD.

Abnormal percent amplitude of fluctuation and functional connectivity within and between networks in benign epilepsy with centrotemporal spikes

BackgroundBenign epilepsy with centrotemporal spikes (BECTS) is one of the most common childhood epilepsy syndromes. The neural basis of BECTS is still poorly understood. This study aimed to further investigate the possible neural mechanisms of BECTS by comparing percent amplitude of fluctuation (PerAF) of resting-state functional magnetic resonance imaging (RS-fMRI) signal of each brain voxel and connectivity within and between related networks in children with BECTS and healthy controls (HCs). MethodsFirstly, we used PerAF method to investigate brain functional alteration and defined the regions of interest (ROIs) where children with BECTS exhibited significant PerAF alterations compared to HCs. We then divided these ROIs into different networks based on previous findings and investigated alterations of functional connectivity within and between networks in children with BECTS. Receiver operating characteristic (ROC) curve was employed to assess the reliable biomarker for distinguishing children with BECTS from HCs based on the intergroup PerAF differences. ResultsChildren with BECTS showed decreased PerAF in the left middle frontal cortex (MFC), right precentral gyrus, left precuneus (PCUN), bilateral posterior cingulate cortex (PCC), left angular gyrus, left inferior parietal lobule (IPL), right supplementary motor area (SMA) and left primary somatosensory cortex (S1) compared to HCs. The IPL and PCC exhibited higher classification power by ROC analysis. Moreover, our findings exhibited increased Intra-network connectivity in the default mode network (DMN), and increased inter-network connectivity of the sensorimotor network (SMN) with Broca's area and DMN. ConclusionsOur study investigated the abnormal PerAF and functional brain networks in children with BECTS, which might provide new insights into the pathological mechanisms of BECTS.

Brain Network Connectivity and Executive Function in Children with Infantile Hydrocephalus.

Introduction: Infantile hydrocephalus (HCP) is a condition in which there is an abnormal buildup of cerebrospinal fluid in the ventricles within the first few months of life, which puts pressure on surrounding brain tissues. Compression of the developing brain increases the risk of secondary brain injury and cognitive disabilities. Methods: In this study, we used diffusion-weighted imaging and resting-state functional magnetic resonance imaging to investigate the effects of ventricle dilatation on structural and functional brain networks in children with shunted infantile HCP and examined how these brain changes may impact executive function. Results: We found that children with HCP have altered structural and functional connectivity between and within large-scale networks. Moreover, hyperconnectivity between the ventral attention and default mode network in children with HCP correlated with reduced executive function scores. Compared with typically developing age-matched control participants, our patient population also had lower fractional anisotropy in posterior white matter. Discussion: Overall, these findings suggest that infantile HCP has long-term effects on brain network connectivity, white matter development, and executive function in children at school age. Future work will examine the relationship between ventricular volumes before shunt placement in infancy and brain network development throughout childhood.

Phase-Amplitude Coupling Brain Networks in Children with Attention-Deficit/Hyperactivity Disorder.

In cognitive neuroscience, there is an increasing interest in identifying and understanding the synchronization of distinct neural oscillations with different frequencies that might support dynamic communication within the brain. This study explored the cross-frequency phase-amplitude coupling brain network characteristics of resting-state electroencephalograms between 30 children with attention-deficit/hyperactivity disorder (ADHD) and 30 age-matched typically developing children. Compared with control group, children with ADHD show increased coupling intensity and altered distribution patterns of dominant paired channels, especially in the δ-γH, θ-γH, α-γH, βL-γH, and βH-γH coupling networks. Regarding graph theory properties, the characteristic path length, the mean clustering coefficient, the global efficiency, and the mean local efficiency significant difference in many cross-frequency coupling networks, especially in the δ-γH, θ-γH, α-γH, βL-γH, and βH-γH coupling networks. The area under the receiver operating characteristic curve (AUC) in low-frequency coupling with a high-gamma frequency was larger than that in coupling with low-gamma frequency (AUC values of δ-γL, θ-γL, α-γL, βL-γL, βH-γL, δ-γH, θ-γH, α-γH, βL-γH, and βH-γH were 0.794, 0.722, 0.666, 0.570, 0.881, 0.992, 0.998, 0.998, 0.989, and 0.974, respectively). These findings demonstrate altered coupling intensity and disrupted topological organization of coupling networks, support the altered brain network theory in children with ADHD. The coupling intensity and graph theory properties of low-frequency coupling with high-gamma frequency were promising resting-state electroencephalogram biomarkers of ADHD in children.

Atypical Resting State Functional Neural Network in Children With Autism Spectrum Disorder: Graph Theory Approach.

Measuring whole brain networks is a promising approach to extract features of autism spectrum disorder (ASD), a brain disorder of widespread regions. Objectives of this study were to evaluate properties of resting-state functional brain networks in children with and without ASD and to evaluate their relation with social impairment severity. Magnetoencephalographic (MEG) data were recorded for 21 children with ASD (7 girls, 60–89 months old) and for 25 typically developing (TD) control children (10 girls, 60–91 months old) in a resting state while gazing at a fixation cross. After signal sources were localized onto the Desikan–Killiany brain atlas, statistical relations between localized activities were found and evaluated in terms of the phase lag index. After brain networks were constructed and after matching with intelligence using a coarsened exact matching algorithm, ASD and TD graph theoretical measures were compared. We measured autism symptoms severity using the Social Responsiveness Scale and investigated its relation with altered small-worldness using linear regression models. Children with ASD were found to have significantly lower small-worldness in the beta band (p = 0.007) than TD children had. Lower small-worldness in the beta band of children with ASD was associated with higher Social Responsiveness Scale total t-scores (p = 0.047). Significant relations were also inferred for the Social Awareness (p = 0.008) and Social Cognition (p = 0.015) sub-scales. Results obtained using graph theory demonstrate a difference between children with and without ASD in MEG-derived resting-state functional brain networks, and the relation of that difference with social impairment. Combining graph theory and MEG might be a promising approach to establish a biological marker for ASD.

Different effects of the DRD4 genotype on intrinsic brain network connectivity strength in drug-na\xefve children with ADHD and healthy controls

The dopamine D4 receptor gene (DRD4) has been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). Recent studies have linked DRD4 to functional connectivity among specific brain regions. The current study aimed to compare the effects of the DRD4 genotype on functional integrity in drug-naïve ADHD children and healthy children. Resting-state functional MRI images were acquired from 49 children with ADHD and 37 healthy controls (HCs). We investigated the effects of the 2-repeat allele of DRD4 on brain network connectivity in both groups using a parameter called the degree of centrality (DC), which indexes local functional relationships across the entire brain connectome. A voxel-wise two-way ANCOVA was performed to examine the diagnosis-by-genotype interactions on DC maps. Significant diagnosis-by-genotype interactions with DC were found in the temporal lobe, including the left inferior temporal gyrus (ITG) and bilateral middle temporal gyrus (MTG) (GRF corrected at voxel level p < 0.001 and cluster level p < 0.05, two-tailed). With the further subdivision of the DC network according to anatomical distance, additional brain regions with significant interactions were found in the long-range DC network, including the left superior parietal gyrus (SPG) and right middle frontal gyrus (MFG). The post-hoc pairwise analysis found that altered network centrality related to DRD4 differed according to diagnostic status (p < 0.05). This genetic imaging study suggests that the DRD4 genotype regulates the functional integration of brain networks in children with ADHD and HCs differently. This may have important implications for our understanding of the role of DRD4 in altering functional connectivity in ADHD subjects.

Disrupted Functional Rich-Club Organization of the Brain Networks in Children with Attention-Deficit/Hyperactivity Disorder, a Resting-State EEG Study.

Growing evidence indicates that disruptions in the brain’s functional connectivity play an important role in the pathophysiology of ADHD. The present study investigates alterations in resting-state EEG source connectivity and rich-club organization in children with inattentive (ADHDI) and combined (ADHDC) ADHD compared with typically developing children (TD) under the eyes-closed condition. EEG source analysis was performed by eLORETA in different frequency bands. The lagged phase synchronization (LPS) and graph theoretical metrics were then used to examine group differences in the topological properties and rich-club organization of functional networks. Compared with the TD children, the ADHDI children were characterized by a widespread significant decrease in delta and beta LPS, as well as increased theta and alpha LPS in the left frontal and right occipital regions. The ADHDC children displayed significant increases in LPS in the central, temporal and posterior areas. Both ADHD groups showed small-worldness properties with significant increases and decreases in the network degree in the θ and β bands, respectively. Both subtypes also displayed reduced levels of network segregation. Group differences in rich-club distribution were found in the central and posterior areas. Our findings suggest that resting-state EEG source connectivity analysis can better characterize alterations in the rich-club organization of functional brain networks in ADHD patients.

Epileptiform discharges relate to altered functional brain networks in autism spectrum disorders.

Many individuals with autism spectrum disorders have comorbid epilepsy. Even in the absence of observable seizures, interictal epileptiform discharges are common in individuals with autism spectrum disorders. However, how these interictal epileptiform discharges are related to autistic symptomatology remains unclear. This study used magnetoencephalography to investigate the relation between interictal epileptiform discharges and altered functional brain networks in children with autism spectrum disorders. Instead of particularly addressing individual brain regions, we specifically examine network properties. For this case-control study, we analysed 70 children with autism spectrum disorders (52 boys, 18 girls, 38–92 months old) and 19 typically developing children (16 boys, 3 girls, 48–88 months old). After assessing the participants’ social reciprocity using the Social Responsiveness Scale, we constructed graphs of functional brain networks from frequency band separated task-free magnetoencephalography recordings. Nodes corresponded to Desikan–Killiany atlas-based 68 brain regions. Edges corresponded to phase lag index values between pairs of brain regions. To elucidate the effects of the existence of interictal epileptiform discharges on graph metrics, we matched each of three pairs from three groups (typically developing children, children with autism spectrum disorders who had interictal epileptiform discharges and those who did not) in terms of age and sex. We used a coarsened exact matching algorithm and applied adjusted regression analysis. We also investigated the relation between social reciprocity and the graph metric. Results show that, in children with autism spectrum disorders, the average clustering coefficient in the theta band was significantly higher in children who had interictal epileptiform discharges. Moreover, children with autism spectrum disorders who had no interictal epileptiform discharges had a significantly lower average clustering coefficient in the theta band than typically developing children had. However, the difference between typically developing children and children with autism spectrum disorder who had interictal epileptiform discharges was not significant. Furthermore, the higher average clustering coefficient in the theta band corresponded to severe autistic symptoms in children with autism spectrum disorder who had interictal epileptiform discharges. However, the association was not significant in children with autism spectrum disorders who had no interictal epileptiform discharge. In conclusion, results demonstrate that alteration of functional brain networks in children with autism spectrum disorders depends on the existence of interictal epileptiform discharges. Interictal epileptiform discharges might ‘normalize’ the deviation of altered brain networks in autism spectrum disorders, increasing the clustering coefficient. However, when the effect exceeds tolerance, it actually exacerbates autistic symptoms.